Stent-Related Adverse Events as Related to Dual Antiplatelet Therapy in First- vs Second-Generation Drug-Eluting Stents

[Background] There are limited data on the long-term stent-related adverse events as related to the duration of dual antiplatelet therapy (DAPT) in second-generation (G2) drug-eluting stents (DES) compared with first-generation (G1) DES. [Objectives] This study sought to compare the long-term stent-related outcomes of G2-DES with those of G1-DES. [Methods] The study group consisted of 15, 009 patients who underwent their first coronary revascularization with DES from the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) Registry Cohort-2 (first-generation drug-eluting stent [G1-DES] period; n = 5, 382) and Cohort-3 (second-generation drug eluting stent [G2-DES] period; n = 9, 627). The primary outcome measures were definite stent thrombosis (ST) and target vessel revascularization (TVR). [Results] The cumulative 5-year incidences of definite ST and TVR were significantly lower in the G2-DES group than in the G1-DES group (0.7% vs 1.4%; P < 0.001; and 16.2% vs 22.1%; P < 0.001, respectively). The lower adjusted risk of G2-DES relative to G1-DES for definite ST and TVR remained significant (HR: 0.53; 95% CI: 0.37-0.76; P < 0.001; and HR: 0.74; 95% CI: 0.68-0.81; P < 0.001, respectively). In the landmark analysis that was based on the DAPT status at 1 year, the lower adjusted risk of on-DAPT status relative to off-DAPT was significant for definite ST beyond 1 year in the G1-DES stratum (HR: 0.42; 95% CI: 0.24-0.76; P = 0.004) but not in the G2-DES stratum (HR: 0.66; 95% CI: 0.26-1.68; P = 0.38) (Pinteraction = 0.14). [Conclusions] G2-DES compared with G1-DES were associated with a significantly lower risk for stent-related adverse events, including definite ST and TVR. DAPT beyond 1 year was associated with a significantly lower risk for very late ST of G1-DES but not for that of G2-DES

Freeze-thaw valves as a flow control mechanism in spatially complex 3D-printed fluidic devices

In this paper, we demonstrate a proof-of-principle of a freeze-thaw valve (FTV) created in a 3D-printed fluidic device. Portions of channels are enveloped by cooling and heating jackets, and a heat transfer liquid is recirculated through the two jackets. A frozen plug is created in selected portions of the target-channel and the heating jacket ensures that a selected temperature is maintained in the rest of the channel. An FTV can be 3D-printed in a wide variety of materials as single piece devices with no moving parts without high resolution requirements of the printing process. Such valves can therefore be incorporated in devices for liquid chromatography or multi-step synthesis process. Computational fluid dynamic simulations of a prototype T-junction piece show the two zones to be well defined at coolant and heating jacket flow-rates greater than 1 mL/min, with power consumptions of 1–3 W. The prototype was printed in Titanium 6Al-4V using selective laser melting and the frozen plug was shown to withstand 20 MPa of pressure. Switching times between states 1 (with a frozen section) and 2 (with both sections thawed) were 0.2–3 min in computational and experimental tests. The scalability of the freeze-thaw system was demonstrated using a multi-gate valve containing 33 junctions without a proportionate increase in operational complexity or switching times

3D printing of porous media at the microstructural scale

What is superficially referred to as ‘packing quality’, a myriad of geometrical parameters governing the interrelations between pores, has only been measured post-hoc in the form of separation efficiency. While several computational studies of chromatography bed microstructures have explored the effects of various packing parameters on dispersion, experimental replication and model validation has remained elusive. Additive manufacturing, or 3D printing, offers the opportunity to manufacture porous media composed of micro-structural elements of different shapes and sizes, and to precisely locate and orient them within the bed. For example, spherical beads with a narrow size distribution can be constructed individually at desired locations within the bed, allowing the creation of specific packing arrangements, i.e. perfectly ordered lattices or random packing mimicking conventionally packed chromatography columns. Further opportunities are to create geometric elements with different shapes or sizes and place them at individual locations within the same bed. Alternatively, the structural focus can shift from the solid-phase to the mobile phase, with the design of complex flow channels within a monolithic bed. These observations led us to propose the use of 3D printing as both a chromatography column production method and as a tool to enable fundamental studies of packed bed microstructures. The main challenges to this approach include achieving sufficient printing resolution to compete with current media in terms of theoretical plate height and developing materials that have appropriate internal porosity and surface functionalities to enable high binding capacity and specificity. Other challenges are as for conventional media, for example good swelling properties, low non-specific adsorption, and the absence of toxicity and leaching. Here, we show examples of progress made to date in creating 3D printed chromatography columns. These include i) micro-structural analyses of columns containing porous beds with a variety of lattice arrangements and channel structures, printed at a maximum current printing resolution of 16 µm and ii) comparison of residence time distributions and flow characteristics for a range of columns, including several printed with different integrated flow distributors and column cross-sections. We demonstrate reasonable fidelity between printed and designed columns and identify current limitations with regard to resolution. Finally, we compare packed beds incorporating deliberately introduced imperfections within packing lattices, including a ‘line defect’ that runs the length of the column and a ‘cluster defect’ consisting of localized voids at various locations within the packing. Experimentally determined reduced plate heights are compared with computational fluid dynamics flow studies

Introduction of Octadecyl-Bonded Porous Particles in 3D-Printed Transparent Housings with Multiple Outlets

Microfluidic devices for comprehensive three-dimensional spatial liquid chromatography will ultimately require a body of stationary phase with multiple in- and outlets. In the present work, 3D printing with a transparent polymer resin was used to create a simplified device that can be seen as a unit cell for an eventual three-dimensional separation system. Complete packing of the device with 5-μm C18 particles was achieved, with reasonable permeability. The packing process could be elegantly monitored from the pressure profile, which implies that optical transparency may not be required for future devices. The effluent flow was different for each of the four outlets of the device, but all flows were highly repeatable, suggesting that correction for flow-rate variations is possible. The investigation into flow patterns through the device was supported by computational-fluid-dynamics simulations. A proof-of-principle separation of four standard peptides is described, with mass-spectrometric detection for each of the four channels separately. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10337-022-04156-w